内科

目的探讨氧化苦参碱对慢性肾脏病（CKD）大鼠血管钙化的改善作用，并分析该作用是否与抑制低氧诱导因子（HIF）-1α、骨形态生成蛋白2（BMP2）及Runt相关转录因子2（Runx2）蛋白表达相关。方法将30只雄性SD大鼠随机分为空白对照组（9只）、模型组（9只）和氧化苦参碱干预组（12只）。模型组和氧化苦参碱干预组通过腺嘌呤灌胃、骨化三醇腹腔注射及高磷饲料喂养建立CKD血管钙化模型；氧化苦参碱干预组在造模同时给予氧化苦参碱（100 mg/kg）灌胃干预。造模第4周末，比较三组大鼠肾脏组织病理学改变（苏木精-伊红染色）、主动脉钙化程度（茜素红S染色）、主动脉组织钙含量、血清HIF-1α水平，以及主动脉HIF-1α、Runx2及BMP2蛋白相对表达量。结果空白对照组肾脏组织结构清晰，肾小球和肾小管形态正常，无明显病理学改变；模型组肾脏组织结构紊乱，肾小球体积缩小，肾小管严重损伤，管腔明显扩张，并可见大量肾小管上皮细胞钙化；氧化苦参碱干预组肾脏组织病理学改变较模型组减轻。空白对照组主动脉未见明显钙化结节；模型组主动脉中膜可见大量棕红色阳性染色，且钙化面积占比大于空白对照组（P<0.05）；氧化苦参碱干预组主动脉中膜棕红色阳性染色较模型组明显减少，钙化面积占比小于模型组（P<0.05）。空白对照组和氧化苦参碱干预组主动脉组织钙含量、血清HIF-1α水平及主动脉HIF-1α、Runx2、BMP2蛋白相对表达量均低于模型组，但氧化苦参碱干预组主动脉组织钙含量及血清HIF-1α水平均高于空白对照组（均P<0.05）。结论氧化苦参碱能有效地减轻CKD大鼠的血管钙化，其作用机制可能与抑制HIF-1α的表达，进而负调控其下游的BMP2/Runx2信号通路，最终抑制血管平滑肌细胞的成骨样表型转分化有关。

Objective To investigate the ameliorative effect of oxymatrine on vascular calcification in rats with chronic kidney disease (CKD), and to analyze whether this effect is related to the inhibition of protein expressions of hypoxia-inducible factor (HIF)-1α, bone morphogenetic protein 2 (BMP2), and Runt-related transcription factor 2 (Runx2). Methods Thirty male SD rats were randomly divided into three groups: blank control group (n=9), model group (n=9), or oxymatrine intervention group (n=12). Rats in both the model group and oxymatrine intervention group were induced to establish the CKD vascular calcification model by intragastric administration of adenine, intraperitoneal injection of calcitriol, and feeding with high-phosphorus diet; those in the oxymatrine intervention group were additionally given oxymatrine (100 mg/kg) by gavage during modeling. At the end of the 4th week of modeling, renal histopathological changes (hematoxylin-eosin staining), aortic calcification degree (alizarin red S staining), aortic tissue calcium content, and serum HIF-1α level, as well as relative expressions of HIF-1α, Runx2, and BMP2 proteins in the aorta, were compared among the three groups. Results In the blank control group, the rats' renal tissue structure was clear, with normal morphology of glomeruli and renal tubules and no obvious pathological changes. In the model group, the rats' renal tissue structure was disordered, the glomerular volume was reduced, the renal tubules were severely damaged with obvious luminal dilation, and massive calcification of renal tubular epithelial cells was observed. The renal histopathological changes in the oxymatrine intervention group were milder than those in the model group. No obvious calcified nodules were found in the aorta of the blank control group; extensive brownish-red positive staining areas were observed in the aortic media of the model group, and the proportion of calcified area was higher than that in the blank control group (P<0.05); compared with the model group, the brownish-red positive staining in the aortic media of the oxymatrine intervention group was markly reduced, accompanied by a notable reduction in the proportion of calcified area (P<0.05). The aortic tissue calcium content and serum HIF-1α level, as well as relative expressions of HIF-1α, Runx2, and BMP2 proteins in the aorta, in the blank control group and oxymatrine intervention group were lower than those in the model group, but the aortic tissue calcium content and serum HIF-1α level in the oxymatrine intervention group were higher than those in the blank control group (all P<0.05). Conclusion Oxymatrine can effectively alleviate vascular calcification in CKD rats. Its mechanism of action may be related to inhibiting the HIF-1α expression, thereby negatively regulating its downstream BMP2/Runx2 signaling pathway and ultimately suppressing the osteoblast-like phenotype transdifferentiation of vascular smooth muscle cells.

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